Arrhythmias and cardiomyopathies panel

Most forms of these conditions follow an autosomal dominant pattern of inheritance with incomplete penetrance and variable severity.

Molecular genetic diagnosis of all arrhythmogenic conditions is based on DNA sequencing of the genes known to be causative (gene panel testing). The analysis and interpretation of the results are carried out on a case-by-case basis. Although the number of genes implicated in arrhythmogenic conditions has expanded considerably in recent years, more than 90% of pathogenic variants in both ion channel disorders and cardiomyopathies are still located in a limited set of major genes, even when comprehensive panels are applied. is the method of choice, as it enables parallel sequencing of both major and minor genes with high analytical depth and now allows reliable screening for exon‑level deletions and duplications across all included genes, thereby achieving the highest possible diagnostic sensitivity.

• In suspected inherited cardiac arrhythmia syndromes, including ion channel disorders and cardiomyopathies, molecular genetic testing can identify the causative pathogenic germline variant and thereby confirm or refine the clinical diagnosis. This is particularly relevant when ECG findings, imaging results, or clinical manifestations are subtle, overlapping, or inconclusive. A molecular diagnosis may support risk stratification, clarify genotype-specific disease mechanisms, and guide individualized management, including cardiac surveillance, pharmacological therapy, avoidance of proarrhythmic triggers or drugs, lifestyle recommendations, and assessment of device-based therapy where appropriate. Therapeutic decisions should always be made by the treating physicians in the context of the patient’s phenotype, family history, and current clinical recommendations.
• Identification of the pathogenic variant in the index patient is essential, as it provides the basis for targeted cascade testing in relatives. In ion channel disorders, predictive testing of at-risk family members, including minors, is often of direct clinical relevance because preventive or therapeutic measures may be indicated before symptoms occur. In cardiomyopathies, predictive testing can identify relatives requiring structured cardiological follow-up and may assist in variant interpretation through segregation analysis. However, particularly in minors, the indication should be carefully considered within genetic counselling, taking into account penetrance, age-dependent disease expression, available preventive options, and the potential psychosocial burden. Molecular diagnosis therefore supports personalized care of the index patient, targeted family evaluation, and informed genetic counselling and family planning.

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